TSLC1和BLU基因在鼻NK/T细胞淋巴瘤中CpG岛甲基化研究

Aberrant DNA methylation of TSLC1 and BLU genes in the promoter CpG Islands in nasal NK/T cell lymphomas

目的了解鼻NK/T细胞淋巴瘤中抑癌基因TSLC1和BLU的甲基化状况,并探讨其在鼻NK/T细胞淋巴瘤发生发展中的作用及与临床病理参数之间的关系。方法应用甲基化特异性PCR(MSP)技术,检测30例鼻NK/T细胞淋巴瘤、10例鼻咽淋巴组织增生中TSLC1和BLU基因启动子区的甲基化状况;应用原位杂交方法对30例鼻NK/T细胞淋巴瘤进行EB病毒检测。结果30例鼻NK/T细胞淋巴瘤中,TSLC1和BLU基因的甲基化频率分别为83.3%(2/530)和50.0%(1/530),且TSLC1和BLU基因中至少有1个抑癌基因发生甲基化的频率为86.7%(2/630);10例鼻咽淋巴组织增生中,2例发生了TSLC1基因甲基化,而BLU基因全部甲基化阴性而非甲基化阳性。未发现TSLC1和BLU基因CpG岛甲基化与EB病毒感染有关。TSLC1和BLU基因启动子区CpG岛甲基化与临床病理特征之间均无统计学相关性(P>0.05)。结论30例鼻NK/T细胞淋巴瘤中多基因的启动子甲基化是一种普遍的事件。两种抑癌基因启动子区CpG岛均具有很高的甲基化频率,表明其在鼻NK/T细胞淋巴瘤的发生发展中具有重要作用,可能对肿瘤的早期诊断及预后评估具有重要意义。

Objective The aberrant promoter hypermethylation status of tumor suppressor genes TSLC 1 and BLU in nasal NK/T cell lymphomas were assessed, and their significant roles in tumorigenesis were explored. Furthermore, we analyzed the relationship between the frequency of TSLC 1 and BLU genes promoter methylation in nasal NK/T cell lymphomas and their clinicopathological parameters. Methods 30 cases of nasal NK/T cell lymphoma and 10 cases of benign nasopharyngeal lymphoid hyperplasia tissues were used for TSLC1 and BLU genes promoter methylation status study with methylation-specific polymerase chain reaction （MSP）. The presence of EBV infection in 30 cases of nasal NK/T cell lymphoma was studied by in situ hybridization. Results The hypermethylation of TSLC1 and BLU gene promoter was detected in 25（83.3 %） and 15 （50 %） out of 30 cases, respectively. Methylation of at least one gene could be detected in 26 out of 30 （86.7%） cases of nasal NK/＇I＂ cell lymphoma. TSLC1 gene promoter CpG island hypermethylation was detected in 2 out of 10 control samples, but no methylation of BLU gene was observed in the same samples. TSLC1 and BLU gene methylation did not correlate with EBV infection. TSLC1 and BLU gene promoter CpG island hypermethylation had no relationship with clinicopathological features. Conclusions Aberrant promoter methylation of TSLC1 and BLU gene, which is a frequent event, may contribute to the malignant progression of nasal NK/T cell lymphoma, and might play important roles in its early diagnosis and prognosis evaluation.